The localization of tumors, such as astrocytomas in the brain in vivo and the determination of the margin between normal tissue and tumor can be useful for surgical, radiotherapeutic and chemotherapeutic approaches to the tumor. Although gliomas generally do not metastasize, they do recur locally after surgical resection and carry a grave prognosis (1). The grave prognosis results in part from the inability to delineate clearly the boundary between tumor and normal brain tissue, and from the restricted permeability of the blood brain barrier to imaging and therapeutic agents. The successful delivery of magnetic resonance contrast agents or of radionuclides for positron or gamma imaging might contribute to the more precise localization of tumor margins.
Monoclonal antibodies prepared against the tumor have been proposed for use in the past as effective carrier molecules for the delivery of contrast and radionuclide agents (2,3). However, the use of such monoclonal antibodies is accompanied by disadvantages. Antibodies are very large molecules that also can carry cross-reactive antigenic determinants that could cause problems. In addition, the monoclonal antibodies seldom bind more than 70% of cells, even in clonogenic tumors.
In addition to monoclonal antibodies, various synthetic polypeptides, such as polylysine which selectively binds to tumor cells as compared to normal brain cells, have been considered for use as carrier agents for therapeutic agents.
Notwithstanding prior efforts, a need still exists for reliable, safe methods for the localization, targeting and treatment of tumors and for complexes that can be used in such methods.